1) Field of Bronchodilator
In the treatment of chronic reversible obstructive respiratory diseases such as bronchial asthma, bronchitis and adult respiratory distress syndrome, air way remission at the time of seizure is important. For such a purpose, bronchodilators are used. Major bronchodilators presently used for clinical purposes may be generally classified into .beta.-stimulants including Salbutamol and xanthine drugs represented by theophylline. The former drugs have a drawback that the effects decrease against intractable diseases, and a deterioration of the symptom due to frequent long-term administration has been pointed out in the treatment of bronchial asthma (The New England Journal of Medicine, vol 321, p. 1517-1527, 1989).
On the other hand, theophylline drugs have a limited use since their safety range is narrow.
2) Field of Antiallergic Drug
Various in vivo chemical mediators are believed to take part in immediate allergy diseases such as bronchial asthma, allergic rhinitis, hives and hey fever. Among them, histamine is one of important mediators, and antihistaminic agents have been used as antiallergic drugs since long ago. However, many of antiallergic drugs of antihistaminic type have central side effects such as drowsiness. For the treatment of asthma, a drug which has not only an antiallergic activity but also a bronchodilator activity will be significant from the viewpoint of the treatment and economy, but a drug having such functions has not yet been clinically developed.
3) Field of Antiplatelet Agent
It is known that platelets play an important role for thrombus formation in connection with a disease state through activation by stimulation, adhesion to vascular walls and aggregation. Various thrombotic diseases caused by thrombus formation include, for example, cerebral thrombosis, pulmonal thrombosis, myocardial infarction, angina pectoris and occlusion of peripheral artery, as main diseases, and all of these diseases require development of useful drugs. As a prophylactic or therapeutic drug, an attention has been drawn to an antiplatelet agent having an inhibitory activity of platelet aggregation. Heretofore, the effect of aspirin has been widely studied, and more recently ticlopidine and cilostazol have been clinically developed. However, a more strongly effective drug is desired in respect of its effects.
In addition to the above-mentioned various thrombotic diseases, there are enumerated various diseases in relation to platelets. Examples of these diseases include nephritis, cancer cell metastasis and the like, and recently various studies have been conducted with regard to prophylactic or therapeutic effects for these diseases achieved mainly by an anti-thrombotic agent having an activity for controlling platelet function ("Journal of Royal College of Physicians", Vol. 7, No. 1, p. 5-18, 1972; "Japan Clinics (Nihon Rinsho)", Vol. 4, No. 6, p. 130-136, 1988; Anticancer Research, Vol 6, p. 543-548, 1986).
Now, the relationship of 5-.omega.-aminoalkyleneoxy or .omega.-aminocarbonylalkyleneoxy substituted benzylamino)-3(2H)-pyridazinone derivatives of the formula (I) and their pharmaceutically acceptable salts according to the present invention with the compounds disclosed in published references will be described.
Compounds of the type wherein a substituted benzylamino group is bonded to the 5-position of a 3(2H)-pyridazinone ring, which are relatively similar to the compounds of the present invention, are disclosed in the following references.
(a) Japanese Patent Publication No. 41455/1994, EP186817B or U.S. Pat. No. 5,098,900 (hereinafter referred to as reference (a)) discloses compounds including 3(2H)-pyridazinone derivatives wherein the 2-position is a lower alkyl group, the 4-position is a chlorine atom or a bromine atom, the 5-position is a benzylamino group having the benzene ring substituted by a substituent including a .omega.-aminoalkyl group, a .omega.-carbamoylalkyleneoxy group, a .omega.-N-mono lower alkylaminocarbonylalkyleneoxy group and an aminocarbonyl group, and their pharmaceutical use as anti SRS-A agents and their pharmacological activities. PA1 (b) Japanese Unexamined Patent Publication No. 030769/1987, EP201765B or U.S. Pat. No. 4,892,947 (hereinafter referred to as reference (b)) discloses compounds including 3(2H)-pyridazinone derivatives wherein the 2-position is a hydrogen atom, the 4-position is a chlorine atom or a bromine atom, the 5-position is a benzylamino group having the benzene ring substituted by a substituent including an alkyloxy group, a .omega.-phenylalkyleneoxy group and a dialkylamino group, and the 6-position is a hydrogen atom, and their pharmaceutical use as anti SRS-A agents and their pharmacological activities. PA1 (c) Japanese Unexamined Patent Publication No. 301870/1988, EP275997B or U.S. Pat. No. 4,978,665 (hereinafter referred to as reference (c)) discloses compounds including 3(2H)-pyridazinone derivatives wherein the 2-position is a hydrogen atom or a lower alkyl group, the 4-position is a chlorine atom or a bromine atom, the 5-position is a benzylamino group having the benzene ring substituted by a substituent including an alkyloxy group, a .omega.-phenylalkyleneoxy group and a dialkylamino group, and the 6-position is a halogen atom, a nitro group, an amino group or an alkoxy group, and their pharmaceutical use as anti SRS-A agents and their pharmacological activities. PA1 (d) WO91/16314, EP482208A or U.S. Pat. No. 5,202,323 (hereinafter referred to as reference (d)) discloses compounds including 3(2H)-pyridazinone derivatives wherein the 2-position is a hydrogen atom or a lower alkyl group, the 4-position is a chlorine atom or a bromine atom, the 5-position is a benzylamino group having the benzene ring substituted by a substituent including an alkyloxy group, a .omega.-phenylalkyleneoxy group wherein the benzene ring may be substituted by an alkyl group or a halogen atom, a .omega.-alkoxycarbonylalkyleneoxy group and a .omega.-aminocarbonylalkyleneoxy group, and the 6-position is an alkyleneoxy group having a various functional group at the .omega.-position, and their pharmaceutical uses as antithrombotic agents, cardiotonic agents, vasodilators and anti SRS-A agents and their pharmacological activities.